Bone marrow transplantation (BMT) has progressed during the past 15 years from a procedure to be undertaken only as a last desperate measure to a therapeutically effective modality for the treatment of selected patients with malignant disease.
As is generally known the dose of most antineoplastic chemotherapeutic agents that may be administered is limited largely by the toxicity to the normal marrow. The availability of donor marrow for transplantation, however, makes it possible to administer chemoradiotherapy in supralethal doses in an effort to kill a greater fraction of the malignant cells and to use the donor marrow to save the patient from iatrogenic death. The infused marrow will reconstitute the host's hematopoietic and immunologic systems. In addition, if the immune system of the transplanted marrow can exert an antitumor effect, marrow transplantation also may represent a form of adoptive tumor immunotherapy.
An autologous marrow graft refers to the patient's own marrow that has been obtained and usually cryopreserved and reinfused after the patient has received supralethal chemoradiotherapy. A syngeneic marrow is obtained from a donor who is a genetically identical twin, and an allogeneic marrow is obtained from a donor of different genetic origin.
Cancer patients are frequently treated by a regimen of high-dose chemotherapy or total body irradiation (TBI) which are used to eradicate the malignant cells. Most preparative regimens have included supralethal TBI because it has an antitumor effect, can penetrate privileged sites for tumor (e.g., CNS and testicle) where chemotherapy is ineffective, and is sufficiently immunosuppressive to allow engraftment.
The most commonly used regimen has consisted of cyclophosphamide (60 mg/kg/day IV) for 2 consecutive days, followed by a supralethal dose of TBI, usually 1000 rad, delivered at 5 to 8 rad/min, or 200 to 225 rad/day for 6 to 7 days. Marrow is infused within 24 hours after the last dose of TBI.
The first 3 or 4 weeks after grafting are critical because the chemoradiotherapy has eradicated all normal marrow function and there is a time lag before detectable cell production by the infused marrow occurs. The granulocyte count usually rises to 500 mm.sup.3 after 2 to 4 weeks. Platelet production generally takes slightly longer. Until that time the patient requires supportive care, with appropriate use of transfusions and antibiotics.